本文選題：尿素通道蛋白B + 基因敲除　； 參考：《吉林大學(xué)》2006年博士論文

【摘要】：尿素通道蛋白(Urea Transporters,UTs)是介導(dǎo)尿素順濃度梯度跨生物膜轉(zhuǎn)運(yùn)的通道蛋白。目前,已克隆出哺乳動(dòng)物的UTs包括UT-A、UT-B兩個(gè)家族。UT-B在腎臟、心臟、腦、睪丸等組織器官有表達(dá),尤其在紅細(xì)胞膜上呈高表達(dá)。雖然,對(duì)UT-B的基因和蛋白結(jié)構(gòu)的研究已經(jīng)取得了顯著成果。但是,對(duì)其生理功能所知有限。因此,為進(jìn)行功能研究建立了UT-B基因敲除模型。已經(jīng)發(fā)現(xiàn)UT-B基因敲除小鼠,因腎內(nèi)尿素逆流交換過程被阻斷而使尿濃縮能力下降,并發(fā)現(xiàn)Jknull表型,即UT-B基因缺失患者的紅細(xì)胞對(duì)2mol/L尿素有溶血抵抗性。 由于對(duì)UT-B基因敲除小鼠其他各臟器與系統(tǒng)的研究甚少,本論文主要針對(duì)雌性生殖系統(tǒng)進(jìn)行研究:來自美國加州大學(xué)UT-B基因敲除種鼠,繁殖后獲得雌性小鼠的基因型與生物特性的研究;探討UT-B基因敲除雌性小鼠生殖延遲原因與機(jī)制;UT-B基因敲除雌鼠生殖腺AQP1和AQP8mRNA表達(dá)及其意義的研究。得出以下結(jié)論:1.成功搭建了一個(gè)UT-B基因敲除小鼠的基因型檢測技術(shù)平臺(tái)。2.UT-B在雌性生殖器官表達(dá),說明UT-B在雌性生殖系統(tǒng)的尿素轉(zhuǎn)運(yùn)中起重要作用。3.UT-B基因敲除雌鼠生殖延遲,并且可作為生殖延遲的動(dòng)物模型。4.4w和6w齡UT-B-/-雌鼠雌激素水平低下,可能是導(dǎo)致UT-B基因敲除雌鼠生殖延遲的直接原因。5.丘腦-垂體-性腺軸異常是生殖延遲的UT-B基因敲除雌鼠雌激素水平低下的原因。6.UT-B基因敲除后水通道蛋白表達(dá)增加,可能是一種代償性的變化。 關(guān)于UT-B基因與蛋白在雌鼠生殖器官與胎盤的表達(dá),以及UT-B基因敲除雌鼠生殖延遲及其機(jī)制的研究發(fā)現(xiàn),在國內(nèi)外均屬首次報(bào)道。本研究的結(jié)果將為雌性生殖延遲的機(jī)制與調(diào)節(jié)提供實(shí)驗(yàn)依據(jù),為進(jìn)一步探討UT-B在生殖系統(tǒng)及神經(jīng)-內(nèi)分泌系統(tǒng)的研究奠定基礎(chǔ)。
[Abstract]:Urea Channel protein (Urea Transporters) is a channel protein that mediates the translocation of urea through biofilm.At present, mammalian UTs including UT-An UT-B family. UT-B is expressed in kidney, heart, brain, testis and other tissues, especially on erythrocyte membrane.Significant results have been achieved in the study of the gene and protein structure of UT-B.However, knowledge of its physiological function is limited.Therefore, the UT-B gene knockout model was established for functional study.UT-B knockout mice have been found to have reduced urinary concentration due to the interdiction of urea countercurrent exchange in the kidney, and Jknull phenotype has been found, that is, the erythrocytes of UT-B gene deficient patients have hemolytic resistance to 2mol/L urea.Due to the lack of studies on other organs and systems in UT-B knockout mice, this paper focuses on the female reproductive system: UT-B gene knockout mice from the University of California, USA.The genotypes and biological characteristics of female mice were obtained after reproduction, and the reasons and mechanism of reproductive delay in female mice with UT-B gene knockout were investigated. The expression and significance of AQP1 and AQP8mRNA in gonad of female mice with UT-B gene knockout were studied.Draw the following conclusion: 1.A platform for genotypic detection of UT-B knockout mice was successfully established. 2. UT-B expression in female reproductive organs, indicating that UT-B plays an important role in urea transport in female reproductive system. 3. UT-B gene knockout female mice are delayed in reproduction.And it can be used as animal model of reproductive delay. 4.4w and 6w old UT-B-r-females have low estrogen level, which may be the direct cause of reproductive delay in UT-B knockout female mice.The abnormal axis of thalamus-pituitary-gonad is the cause of the low estrogen level in the reproductive delayed UT-B knockout female. 6. The increase of aquaporin expression after the knockout of UT-B gene may be a compensatory change.The expression of UT-B gene and protein in female reproductive organs and placenta, and the reproductive delay and its mechanism of UT-B gene knockout in female mice are reported for the first time at home and abroad.The results of this study will provide experimental basis for the mechanism and regulation of female reproductive delay and lay a foundation for the further study of UT-B in the reproductive system and neuroendocrine system.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R363

【引證文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 張學(xué)新;尿素通道蛋白B基因敲除小鼠心臟電生理特性的改變及其機(jī)制研究[D];吉林大學(xué);2007年

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本文編號(hào)：1768192